Myocardial Energy Metabolism
The cardioprotective effect of exercise is attributable to improved myocardial glucose and lipid metabolism, as well as enhanced adaptive increase of mitochondrial biogenesis, which is accompanied by PGC-la activation. It is known that the autophagy is induced in the acute phase of MI as an adaptive response of the heart to protect itself from cardiac injury [32, 33].
However, long-term exercise training significantly reduces myocardial infarct size and abolishes the induction of autophagy in mice with AMI, which might be an important phenomenon of reduced myocardial injury due to exercise activity. The increased apoptosis is a hallmark of the loss of cardiomyocytes during AMI [34, 35]. It has previously been demonstrated that Bax deficiency or Bcl-2 overexpressingmice displayed reduced infarct size after MI [36, 37].
Cardiac ischemia has a strong influence on myocardial glucose and fatty acid metabolism . The upregulation of GLUT-1 has been widely demonstrated in acute myocardial ischemia with and without reperfusion [, 39], although the expression of GLUT-4 could be either upregulated  or downregulated  due to different animal models of myocardial ischemia. Meanwhile, we found that GSY1, an enzyme involved in glucose metabolism, was also induced in mice subjected to LCA ligation.
In addition to increased glucose uptake and metabolism, the downregulation of genes encoding enzymes involved in fatty acid metabolism has previously been reported in hearts with AMI [27, 28].
Genes encoding enzymes of glucose and fatty acid metabolism are transcriptionally regulated by PPAR . Although some studies fail to show a cardioprotective effect of PPAR activation in myocardial ischemia , some lines of evidence indicates that agonists of PPAR-a or PPAR-y are beneficial to protect the heart from ischemia injury . These data indicate that long-term exercise training could be an effective way to improve cardiac glucose and fatty acid metabolism in AMI, although the potential roles of PPAR-a and PPAR-y need to be further elucidated. A decline in mitochondrial biogenesis and function plays a key role in the development of heart failure after MI .
Of note, previous studies particularly focused on the mitochondrial impairment during the late stage of MI e. These data reveal that mitochondria might have a rapid adaption to AMI through increasing mtDNA replication and transcription. Furthermore, we demonstrated that long-term exercise training could further enhance mtDNA biogenesis in mice with AMI.
Knowing that the impaired mitochondrial biogenesis is a central mechanism responsible for myocardial injury following MI, we propose that the early change of mitochondrial replication and transcription might probably be a beneficial response in the acute phase of MI which could be further enhanced by exercise. PGC-la is a master transcriptional regulator of mitochondrial biology, which can be induced by exercise . However, it has also been reported that PGC-la could be induced and detected in the blood samples of patients 72 h after the onset of an ST-segment elevation AMI, which is supposed to be a cellular response to AMI and probably serves as a potential marker for cardiac recovery capacity after AMI .
In the present study, we found that the enhanced mitochondrial biogenesis in the acute phase of AMI was accompanied with an induction of PGC-la. Importantly, the AMI-induced upregulation of PGC-la could be further enhanced by exercise, suggesting that long-term exercise might be beneficial to enhance the early adaptive response of mitochondrial biogenesis in the acute phase of AMI which might be related to an upregulation of PGC-la.
It has to be mentioned that the protective effect of exercise against the acute myocardial injury following AMI should be more complex than involving myocardial energy metabolism and mitochondrial biogenesis. It has recently been reported that telocytes, a novel interstitial cell type, with extremely long and thin processes, play important roles in tissue repair and regeneration . Telocytes have been found to be decreased in myocardium during AMI and increased number of telocytes was beneficial to induce angiogenesis and reduce myocardial infarction .
Besides that, although the current study shows that. Finally, though we have showed data based on TUNEL stainings, it would be interesting to use PI uptake to show directly cell death differences in the future. In summary, the present study shows that long-term exercise training exerts cardioprotective effects to reduce infarct size and attenuates cardiomyocyte apoptosis and autophagy in the acute phase of AMI.
Furthermore, exercise training improves myocardial glucose and lipid metabolism and further enhances the adaptive increase of mitochondrial biogenesis in response to AMI which is accompanied by an induction of PGC-la.
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Further knowledge on the molecular mechanisms that mediate protective effects of exercise against AMI might enable us to develop novel pharmacological strategies to salvage cardiac function in the acute phase of AMI. World J Cardiol ; Mol Cell Biochem ; Am J Med Sci ; Antioxid Redox Signal ; Biomed Rep ; Cell Physiol Biochem. Heart Br Card Soc ; Prog Cardiovasc Dis ; Am Heart J ; Circulation ; Cardiovasc Res ; Med Sci Sports Exerc ; J Appl Physiol ; Free Radic Biol Med ; Physiol Bethesda Md ; Circ Res ; J Mol Cell Cardiol ; Physiol Res ;SS PloS One ;9:e Cell Biochem Biophys ; Physiol Rev ; J Mol Cell Cardiol ; J Clin Invest ; Pharmacol Ther ; Life Sci ; Lab Investig ; Int Heart J ; PloS One ;6:e J Cell Mol Med ; J Cell Mol Med ; Karger AG, Basel www.
Karger AG, Basel L.
Tao, Y. Bei and S. Lin contributed equally to this work.
Myocardial energy metabolism during ischemia and the mechanisms of metabolic therapies.
Materials and Methods This study was approved by the ethical committees of the Nanjing Medical University and all animal experiments were conducted under the guidelines on humane use and care of laboratory animals for biomedical research published by National Institutes of Health No. Tunel staining Heart tissues were harvested and embedded with paraffin.
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